Synthesis And Anticonvulsant Activity Evaluation Of-Alkyl-[1,2,4]Triazolo[4,3-A]Quinoxaline-4(5H)-one

In order to find the risk-benefit ratio of new anti-epileptic drugs, A series of5-alkyl-[1,2,4]triazolo[4,3-a]quinoxaline-4(5H/)-one (7a-7u) were designed and synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test with intraperitoneally injected in mice. And the compound (7d) showed a strong antagonist activity Attachment for oral administration experiments, the measured time-course of compound (7d)(100mg/kg) in the MES test for oral administration. The pharmacology results showed that most of the compounds synthesized exhibited positive anticonvulsive activity. Among which,5-hexyl-[1,2,4]triazolo[4,3-a]quinoxaline-4(5H)-one (7d) was the most potent with ED50value of27.39mg/kg and protect index (PI=TD50/ED50) value of24.99. Besides the anti-MES efficacy, the potency of compound (7d) against seizures induced by pentylenetetrazole and bicuculline were also established, which suggested that the mechanisms of action including enhancing of GABAergic activity might be involved in its anticonvulsant activity.